Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim

Phase 3

Completed

Conditions: Breast Cancer
Chemotherapy-induced Neutropenia

Interventions: Drug: LA-EP2006
Drug: Neulasta®

Registration Number: NCT01516736

Lead Sponsor: Sandoz

Brief Summary: The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Detailed Description: The Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare the proposed biosimilar LA-EP2006 with the reference pegfilgrastim in woman with early stage breast cancer receiving (neo)-adjuvant myelosuppressive chemotherapy. Patient received TAC (intravenous docetaxel 75mg/m\^2, doxorubicin 50 mg/m\^2, and cyclophosphamide 500mg/m\^2) on day1 of each cycle, for six or more cycles. A total of 308 patients were randomized to LA-EP2006 (n=155) or reference Neulasta® (n=153). Treatment was given subcutaneously on day 2 of each cycle. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count \<0.5 × 10\^9 cells/L). LA-EP2006 was equivalent to the reference product in DSN (difference: -0.16 days; 95% CI \[-0.40, 0.08\]). Further, LA-EP2006 and the reference pegfilgrastim showed no clinically meaningful differences regarding efficacy and safety.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 308

Inclusion Criteria

histologically proven breast cancer
eligible for six cycles of neoadjuvant or adjuvant chemotherapy

Exclusion Criteria

concurrent or prior chemotherapy for breast cancer
concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy, immunotherapy, monoclonal antibodies, and/or biological therapy
concurrent prophylactic antibiotics
previous therapy with any G-CSF (granulocyte-colony stimulating factor) product

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LA-EP2006	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.
Neulasta®	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.

Primary Outcome Measures

Name	Time	Method
Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy	21 days (Cycle 1 of chemotherapy treatment)	Mean duration of severe neutropenia, defined as number of consecutive days with ANC \<0.5 × 10\^9/l (grade 4 neutropenia).

Secondary Outcome Measures

Name	Time	Method
Incidence of Febrile Neutropenia (FN)	across all cycles (18 weeks)	FN was defined as oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) \< 0.5 × 10\^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.
Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles	across al cycles (18 weeks)	Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once.
Mortality Due to Infection	Study course (19 weeks)	Number of patients with death due to infections
Time to ANC Recovery in Days in Cycle 1	across Cycle 1 (3 weeks)	Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10\^9 cells/L after the nadir in Cycle 1.
Depth of ANC Nadir in Cycle 1	Cycle 1 (3 weeks)	The depth of ANC nadir was defined as the patient's lowest ANC (10\^9 cells/L) in Cycle 1.
Number of Patients With ANC Nadir Per Day in Cycle 1	Cycle 1 (3 weeks)	Numbers of patients with ANC nadir based per day during Cycle 1 are given.
Frequency of Infections by Cycle and Across All Cycles	across all cycles (18 weeks)	The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".